3820
Macromolecules 1992,25, 382Ck-3824
Communications to the Editor Living (Co)polymerization of Adipic Anhydride and Selective End Functionalization of the P a r e n t Polymer
Table I Polymerization of AA Initiated by Al(O*Pr)sin Toluene at 20 O C . Dependence of Experimental if&, on Reaction Time ([AA] = 0.6 M, [AA]/[Al]o = 21)
N.Ropson, Ph. Dubois, R. Jerome,' and Ph. Teyssie 29 36 87
Center for Education and Research on Macromolecules (CERM), University of Li2ge, Sart Tilman B6, B-4000 Li2ge, Belgium Received December 11, 1991 Revised Manuscript Received March 13, 1992
Introduction. The availability of erodible and biocompatible materials, such as aliphatic polyanhydrides, is also of great interest for controlling the kinetics of the release of drugs.lV2 Polycondensation of mixed anhydrides is the traditional method3-5 of synthesis of polyanhydrides, which has all the drawbacks of a step-growth polymerization. Although the ring-opening polymerization of alicyclic anhydrides is most likely the best way of avoiding these drawbacks, some previous publications6J have reported that the ring-opening polymerization of adipic anhydride (AA or oxepan-2,7-dione) is not under complete control of molecular mass and polydispersity (eq 1).
n
41
ZnClz(lw%) CH2Cl2,t t . 6 h
14
OC(CH2)4C
gn= 1700; &dMn
\
--0
0
= 1.7: yield = 75%
R
R ( $ b
/
Al-
o
-
~
0
II
R0-c7
ro
1
/
*
ro
1
of the polyester is systematically an alcohol (after hy-
* To whom correspondence should be addressed.
700 850 2250
drolysis of the growing species),and the second extremity is quantitatively capped by an ester, the alkoxy radical of which is nothing but the alkoxy group of the initiator. Similarly, functional aluminum alkoxides have proven to be very successfulin the synthesis of end-reactive PCLlO and PLA." This paper will also report the polymerization of AA as initiated by functional aluminum alkoxides, the structure of which is schematized below.
il
c, R = (CHz)2OC
(1)
This paper aims at reporting preliminary results on the living polymerization of adipic anhydride as initiated by aluminumalkoxides. Aluminum isopropoxide has proven to be very effective in the formation of poly(€-caprolactone) (PCL)E and polylactides (PLA)g with a predictable molecular mass. The "coordination-insertion" mechanism which is operative is schematizedby eq 2. One end group ,AI-
780 969 2338
'C=CH, Me'
n
0
3 4 24
Experimental Part. Oxepan-2,7-dione was prepared as described elsewhere.l2 e-Caprolactone was dried over calcium hydride for 48 h at room temperature. The preparation of diethylaluminumalkoxides and aluminum trialkoxides has been described in detail previously.10J3 Polymerization was carried out under stirring in toluene, in a previously flamed and nitrogen-purged glass reactor. Polymerization was stopped by adding a large excess of petroleum ether, and the precipitated PAA was recovered by filtration. The polymer was dissolved in asmall volume of chloroform and added with an aqueous EDTA solution in order to remove the catalyst residues by repeated extractions. The polymer solution was washed with water up to neutral pH, concentrated under reduced pressure, and finally poured into ether (or heptane) with precipitation of PAA. lH NMR spectra of PAA were recorded in CDCL using a Bruker AM 400 apparatus. IR spectra were recorded on a Perkin-Elmer 1600 Series FTIR apparatus. Results and Discussion. Monomeric Adipic Anhydride Synthesis. Depolymerization of poly(adipic anhydride) was reported by Hill14 as an effective way to prepare oxepan-2,7-dione. Adipic acid was convertad with acetic anhydride into a "mixed adipic anhydride" (MAA), which was then step-polymerized (eq 3). The formed polyanhydride was depolymerized under vacuum in the presence of zinc acetate.12 The yield was on the order of 70% as compared to 50% in the absence of catalyst. The 1HNMR spectrum of the monomer in CDCb shows a triplet at 2.8 ppm and a multiplet at 2.0 ppm in a 1:l ratio, which is in agreement with the expected structure.6 The infrared spectrum shows a doublet at 1800 and 1753
0024-929719212225-3820$03.00/0 0 1992 American Chemical Society
Macromolecules, Vol. 25, No.14, 1992
Communications to the Editor 3821 a
a ' b a
L a b b a d ' '
C
d
I'rntnnr a
n'
b C
2.20
d
1.25
e
I
I
I
5.2
5.0
L.8
a'
CDCI3
I
-
A
I
I
8.0
7.0
I
I
5 .O
6.0
L.0
3 .o
2 0
10
PP M
Figure 1. lH NMR spectrum of PAA as initiated by Al(OiPr)3(solvent = CDClS). Table I1
lH NMR Chemical Shifts of Functionalized PAA As Initiated by Al(O'Pr)S, 2a, lb, and IC chemical shift 13 (intensity)
X-R-O
(CHdzCHO b a BrCHzCHzO (2a) b a CHpCHCH~CH~CHzO (lb) e d c b a ~,e
H, 4.9 (0.1) 4.39 (0.25)
Hc
Hb
4.06 (0.7) 4.35 (12)
jLH,cHp
Hd
H.
1.2 (0.6) 3.52 (0.3) 2.15 (0.4) 1.95 (9.9)
5.8 (0.2) 5.65 (3.1)
5.02 (0.4) 6.15 (2.8)
CHzCOOH 2.2 (0.2) 2.2 (0.3) 2.25 (0.55) 2.2 (6.0)
Mdexptl) 2032
2430 2410 2550
(1C) H/c=c\cM, d
a
C
cm-l, which is characteristic of a cyclic anhydride, and a second doublet characteristic of the cycle at 961 and 985 cm-1. 0
11
0
11
HOC(CH&COH adpic acid
2(CHaCO)fl reflux
00
IIII
0 0
IIII
CH~COC(CHZ)&OCCH~
+
0
XHjCOOH
initiated by aluminum isopropoxide was first studied in toluene at 20 OC. The experimental molecular weight as measured by lH NMR (from comparison of the signal intensity of the acarboxyl methylene end group [-CH&OOHl and the aanhydride methylene in the polyanhydride chain [-CH&(O)OC(O)-l) increases linearly with monomer conversion (Table I). Avery close agreement is also observed between the experimental and the theoretical molecular weight calculated as
"mixed adipic anhydride' (MAA)
M A A
140 4: (0.Qrrbar)
(4)
m
f
(CH3COCWn e
n
> 240 1:(0.Qmbpr)
adipic anhydride (AA)
Adipic Anhydride Homopolymerization Initiated by Al(0iPr)S. The polymerization of oxepan-2,7-dione
where x = degree of conversion (9% 1, n = number of active sites per aluminum molecule, [MI/[All = monomer to initiator molar ratio, and 128 = molecular mass of AA. When n is supposed to be 1, the relationship between
M,(theor) and M,(exptl) is linear and goes through the origin (least-squares linear regression coefficient,0.997). All these observations are consistent with the living character of the chain propagation. In toluene at 20 "C, only one of the three Al-alkoxy bonds of the initiator thus participates in the polymeri-
3822 Communications to the Editor
Macromolecules, Vol. 25, No. 14, 1992
9
4.75 9.90
b. a
I Figure 2.
NMR of PAA as initiated by Et&[O(CH2)20COC(CH3)=CHzl
1H
(IC)(solvent = CDC13).
Table I11 Polymerization of AA As Initiated by Aluminum Alkoxidee 2a, lb, and IC in Toluene poly" conditions initiator Al(OCH&H2Br)s (2a) E~QAIO(CH~)~CH=CH~ (lb) 0 II
T ("C) 20 35 35
time (h) 24 40 40
(AA)/(Al)(theor) 23 23 23
convn ( % ) 85 82 84
~
M,(theor) 2550 2460 2520
_
_
Mdexptl) 2430 ~. . ~
2410 2550
EtzAD(CHz)zO~
\
,C=CH, CH3
zation (n = 1). In the absence of Al(OiPr)3,no polymerization occurs. The obtained poly(adipicanhydride) was characterized by 'H NMR analysis. The spectrum is reported in Figure 1and shows a triplet at 1.75 ppm and a multiplet at 2.50 ppm. Chemical shifts characteristic of the anhydride are thus shifted to lower ppm values, which is consistent with the ring opening of 0xepan-2,7-dione.~ When the AA polymerization is initiated by aluminum isopropoxide, one end group of PAA is systematically an acid function which results from the hydrolysis of the growing species (6[CHzCOzHl = 2.2 ppm), whereas the second extremity is quantitatively capped by an isopropyl ester group (G[COCH(CH&] = 5.0 ppm; G[COCH(CH3)zI = 1.25 ppm), the isopropyloxy radical of which is nothing but the alkoxy group of the initiator. The infrared spectrumshow a doublet at 1816and 1759 cm-l, which is characteristic of an aliphatic anhydride. Furthermore, it confiims the complete diaappearance of the doublet centered on 970 cm-l and characteristic of the ring vibration of a cyclic anhydride, supporting the hypothesis that the ring opening of the monomers has 0~curred.l~
All these experimental results support a polymerization which proceeds through "coordinative-insertion" of the monomer into the "Al-0" bond of the initiator and involves the selective cleavage of one oxygen-carbonyl bond of the AA (eq 5). OR
r
OR
1
Selective End Functionalizationof PAA. According to the previous section one end group of PAA is an acid and the second extremity is capped by an ester, the alkoxy
Communications to the Editor 3823
Macromolecules, Vol. 25, No.14, 1992
CH:
b
c
d
3
l
l
l
l
l
CH, 'CH-0
CH/
l
.
l
l
l
l
.
L.0
5.0
6.0
l
l
PPM
l
l
l
l
l
l
l
3.0
l
,
.
I
2.0
1
1.0
Q -C- (CH,),O c
b
d
II
d f
e
h
i
m
i
g'
a C
I
6.0
,
.
,
,
,
5.0
.
,
,
,
I
'.O
,
,
PPM
I
3.0
,
,
,
,
I
2.0
,
,
,
,
I
.
1.0
Figure 3. 'HNMR spectra of (a) the PrO-PCL-OH block and (b) the block copolymer P[CL-b-AA]a-isopropyl ester, w-carboxylic acid (solvent = CDCld. radical of which is the alkoxy group of the initiator. Accordingly, functional aluminum alkoxides (1 and 2)are acid, w-Xfunctionalpolyexpected to produce CY-carboxylic anhydrides, X being the organic function associated to the active alkoxide. 'H NMR analysis supports the expectation in the particular case where the AA polymerization has been initiated by Al[O(CH&Br]3 (2a),Et,&l[O(CH&CH=CHz] (lb), and Et2A1[O(CH2)20C(O)C(CH3)=CHzl(IC), respectively (Figure 2, with IC). In addition to the assignment of the methylene protons of the chain, Table I1 reports the chemical shifts and intensities of the CY-carboxylic methyleneprotons and those characteristic of the 2-bromoethyl, 4-pentenyl, and 2-(methacryloy1oxy)ethyl end groups, respectively. The close agreement between the theoretical molecular weights (as calculated from eq 4 where n = 1) (Table 111) and the experimental values determined by lH NMR (integration of signals at 2.2 and 1.75 ppm, reapectively) unambiguously shows that the functional group associated to the active alkoxy groups of Al is selectively attached to one chain end. These
experimental data are again in favor of the living polymerization of AA under very mild conditions and confirm the formation of asymmetrictelechelic polyanhydrides in a perfect analogy with the t-CL and lactide polymerization.10Jl Block Copolymerization of c-CLand AA. In block copolymerization experiments, the t-CL polymerization has been first initiated by Al(OiPr)3in toluene at 20 O C . After 5 h of polymerization,a sample of PCL is withdrawn from the reactor, and the molecular weight is determined by GPC and 'H NMR ( M n = 6000). A carefully dried AA solution is then added to the living polycaprolactone solution, and the temperature is raised up to 80 OC. After 36 h, the polymerization medium is acidified at room temperature and the crude copolymerization product analyzed by SEC and 'H NMR. The size-exclusion chromatogram in THF (a selective solvent of PCL) shows one elution peak with a slight increase of M;, and no change in polydispersity (MW/Mn = 1.25). The crude copolymerization product has been fractionated by using cold THF (
